What is the recommended dose of keto‑analogues (e.g., Ketosteril) for an adult with chronic kidney disease stage 3‑5 not on dialysis who is following a protein‑restricted diet of approximately 0.6 g/kg/day?

Ketoanalogue Dosing in CKD Stage 3-5

For adults with CKD stage 3b-5 (eGFR 15-45 mL/min/1.73 m²) following a protein-restricted diet of approximately 0.6 g/kg/day, prescribe ketoanalogues at 1 tablet per 5 kg body weight daily (typically 9-14 tablets of Ketosteril® for most adults), targeting total protein equivalents of 0.55-0.60 g/kg/day when combined with dietary protein. 1

Standard Dosing Protocol

The recommended ketoanalogue dose is 1 tablet per 5 kg body weight per day, which translates to approximately 9-14 tablets daily for a typical adult. 1, 2 This dosing applies specifically to Ketosteril®, the most commonly studied formulation. 3

Dietary Integration

• Dietary protein intake should be 0.3-0.4 g/kg/day when using the very-low-protein diet (VLPD) approach, though it may be increased up to 0.6 g/kg/day for tolerability. 1, 4
• Total protein equivalents (dietary protein + ketoanalogue supplementation) must reach 0.55-0.60 g/kg/day to prevent malnutrition. 1, 4
• Energy intake must be 30-35 kcal/kg/day to maintain nitrogen balance and prevent protein-energy wasting. 1, 2

Patient Selection Criteria

Only metabolically stable adults with CKD stage 3b-5 who can adhere to strict dietary restrictions under close supervision are appropriate candidates. 1, 4

Absolute Contraindications

• Metabolically unstable patients (acute illness, uncontrolled diabetes, active catabolism) must never receive ketoanalogue therapy. 1, 4
• Children with CKD are contraindicated due to growth impairment risk. 1, 4
• Frail older adults with sarcopenia require higher protein targets and should not receive VLPDs. 1, 4
• Hospitalized patients with acute illness should discontinue therapy as protein requirements increase. 1, 4

Special Considerations for Diabetic CKD

Diabetic patients generally require higher protein intake (0.6-0.8 g/kg/day) and are less suitable candidates for very-low-protein diets with ketoanalogues. 1, 4 The KDOQI 2020 guideline provides only opinion-level (not evidence-based) recommendations for ketoanalogue use in diabetic CKD, whereas it gives Grade 1A evidence for non-diabetic patients. 1

• For diabetic stage 5 CKD, KDIGO 2024 recommends maintaining 0.8 g/kg/day protein intake without ketoanalogues as the preferred approach for most patients. 1
• Ketoanalogues may be considered in diabetic patients only when metabolically stable and under intensive supervision by both nephrologist and renal dietitian. 1

Implementation Requirements

Mandatory involvement of a registered renal dietitian is essential for initial counseling, education, and ongoing dietary support. 1, 4 This is not optional—the complexity of VLPD requires expert guidance to prevent malnutrition.

Monitoring Protocol

• Nutritional assessment every 3 months: appetite, dietary intake, body weight, BMI, serum albumin. 1
• Renal function monitoring: eGFR, serum creatinine, and urea at baseline and months 3,6,9, and 12. 1, 2
• Metabolic parameters: serum potassium, phosphorus, calcium, bicarbonate, and parathyroid hormone regularly. 1, 5

Expected Clinical Outcomes

Ketoanalogue-supplemented VLPDs delay dialysis initiation by approximately 1 year compared to conventional low-protein diets alone. 1, 6 The rate of GFR decline is reduced by 57% with ketoanalogue therapy. 6

• Short-term dialysis risk decreases significantly: 6.8% versus 10.4% at one year in stage 4 CKD patients continuing ketoanalogues. 3
• GFR improvement occurs between 3-12 months of therapy in many patients. 1, 2
• Urea nitrogen levels decrease by 6 months without compromising nutritional status. 1, 2
• BMI and serum albumin remain stable, indicating preserved nutritional status. 1, 2, 5
• Calcium-phosphate homeostasis improves: serum phosphorus decreases and calcium increases. 5

Number Needed to Treat

The NNT to postpone dialysis is 22.4 for patients with eGFR <30 mL/min/1.73 m², but improves dramatically to 2.7 for those with eGFR <20 mL/min/1.73 m². 1 This suggests greater benefit in more advanced CKD.

Critical Pitfalls to Avoid

Very-low-protein diets without ketoanalogue supplementation (≈0.3 g/kg/day) increase mortality (hazard ratio 1.92; 95% CI 1.15-3.20). 4 Never prescribe protein restriction below 0.6 g/kg/day without ketoanalogue supplementation.

• Do not reduce protein below 0.8 g/kg/day without proper nutritional counseling and monitoring—this significantly increases malnutrition risk. 4
• Use adjusted body weight for calculations, not fluid-overloaded weight. 1
• Address sodium, phosphorus, and potassium intake simultaneously—do not focus solely on protein restriction. 1, 4
• Discontinue therapy during acute illness or hospitalization when protein requirements rise. 1, 4

Alternative Approach for Most Patients

For the majority of CKD stage 3-5 patients who are not at imminent risk of kidney failure or cannot adhere to strict dietary restrictions, KDIGO 2024 recommends a simpler approach of 0.8 g/kg/day protein intake without ketoanalogues. 1, 4 This provides adequate nutrition with less intensive monitoring and is more practical in real-world settings where renal dietitian access may be limited. 1